Gliflozin-Derived SGLT2 Inhibitors: Recent Advances and Future Perspectives in the Management of Type 2 Diabetes

Gliflozin derivatives, a class of Sodium-Glucose Cotransporter (SGLT) inhibitors, have emerged as effective antidiabetic agents offering notable cardiovascular and renal protection. This class of compounds inhibits glucose reabsorption in the kidneys, thereby improving overall glycaemic control. This review provides a comprehensive overview of gliflozin derivatives, emphasizing their chemical characterization, safety, therapeutic efficacy, pharmacokinetic analysis, and potential future applications, focusing on clinical trials and new developments released between 2010 and 2026. Gliflozin derivatives slow the progression of chronic kidney disease and reduce the risk of heart failure. Some preliminary experimental evidence has reported the antibacterial activity of canagliflozin against MRSA. The Gliflozin derivatives dapagliflozin (IC50 =1.1nM), ertugliflozin (IC50 =0.9nM), sotagliflozin (IC50 =1.8nM), and bexagliflozin (IC50 =2.3nM), which has core motif, 1-chloro-2-(4-alkoxy benzyl) benzene as an aglycon unit and a glycon unit bind with SGLT2 receptor and lowered the HbA1c by 1.2%, 1.7%, 0.41% and 0.80%, respectively. Its selectivity, pharmacokinetics, and toxicity profiles are also optimal. Recent studies have demonstrated their involvement in conditions other than diabetes, including obesity, non-alcoholic fatty liver disease, Cardioprotective, Nephroprotective, Anti-inflammatory, and antihypertensive effects. Gliflozin derivatives represent a paradigm shift in the management of diabetes and have broad therapeutic potential. Future studies should emphasize creative structural changes to increase safety and efficacy.